Sebaceous glands contain undiferentiated stem cells and highly-differentiated, lipid-laden cells. Synthesis of this lipid in the differentiated cells is associated with high levels of fatty acid synthetase and malic enzyme. Another characteristic of the differentiated cells is a high concentration of lysosomes. These organelles contain the hydrolases which partially digest the cells during holocrine secretion. The undifferentiated stem cells, on the other hand, appear to lack both lipogenic enzymes and lysosomes. We propose to use fatty acid synthetase, malic enzyme and lysosomes as markers for the differentiated state. Using autoradiographic immunocytochemical and biochemical techniques, we will study how the concentrations and rates of synthesis of these proteins are regulated, when and where accumulation of enzyme and lysosomes is initiated and the nature of the stimulus which initiates differentiation. We further propose to establish the stem cells in culture in order to study the differeniation process under defined conditions. The avian sebaceous or uropygical gland is large and well-defined. In addition, the initial accumulation of lipogenic enzymes occurs beofore hatching, 2 or 3 days after the gland is morphologically identifiable. This tissue is thus particularly well-suited as a model for studies of the regulation of holocrine secretion. Understanding of the molecular mechanisms which control cell proliferation and lipid synthesis in sebaceous glands may provide a rational basis for the development of drugs to control acne. In addition, this study should provide basic information on the regulation of the committment to differentiation and on regulation of the lipogenic enzymes in a non-hepatic tissue.